Background: Knowledge and reported self-care practices of postpartum women are important for early detection, prevention and treatment of puerperal sepsis. Objectives: This study analyzes the knowledge and self-care practices for prevention of puerperal sepsis and their determinants among postpartum women. Methods: A hospital-based analytical cross-sectional study which included 343 postpartum women was conducted from February to March 2021. Data were collected using interviewer-administered questionnaire. Predictors of knowledge and self-care reported practice were determined using binary logistic regression. p < 0.05 was considered significant. Results: More than half ( n = 213, 62.1%) of the postpartum women had adequate knowledge on prevention of puerperal sepsis. Only 39 (11.4%) of the women reported adequate self-care practices toward prevention of puerperal sepsis. Secondary education (adjusted odds ratio = 0.18, 95% confidence interval = 0.06–0.49, p = 0.001), tertiary education (adjusted odds ratio = 0.52, 95% confidence interval = 0.19–1.38, p = 0.021) and getting information from healthcare providers (adjusted odds ratio = 1.06, 95% confidence interval = 0.55–2.06, p = 0.049) were significant determinants of knowledge on prevention of puerperal sepsis. Also, secondary education (adjusted odds ratio = 0.11, 95% confidence interval = 0.04–0.30, p = 0.001), tertiary education (adjusted odds ratio = 0.16, 95% confidence interval = 0.06–0.39, p = 0.001), and having more than four antenatal care visits (adjusted odds ratio = 1.21, 95% confidence interval = 0.49–3.27, p = 0.041) were significant determinants of reported self-care practices for prevention of puerperal sepsis. Conclusion: A significant gap in reported self-care practices to prevent puerperal sepsis was evidence. Secondary and tertiary education were significant predictors for both knowledge and self-care reported practices. Special attention should be given to women with low education level.
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